Secologanine derived alkaloid

The synthesis of dihydromeroquinene derivatives from secologanin (268) affords a new and convenient stereoconservative synthesis of the Cinchona alkaloids. Two routes were developed (Scheme 44) both resulted in the conservation of the easily epimerised centre at C-2 in the secologanin derivatives. The first route resulted in the formation of dihydromeroquinene (cincholoipon) hydrochloride (269), which was identified by conversion into methyl N-benzoyldihydromeroquinenate (270) the other afforded methyl dihydro-meroquinenate (271), which has previously been converted into quinine. 

Monoterpenoid indole alkaloids (MIAs) are derived from tryptophan metabolism. MIAs are one of the most structurally diverse class of compounds with over 2,000 structures. They are mostly found in the Apocynaceae, Loganiaceae, and Rubiaceae family of plants [12]. Similar to BIA biosynthesis, the committed step of MIA biosynthesis begins with the condensation of tryptamine (derived from tryptophan) and secologanin (derived from terpene biosynthesis) to form strictosidine... 

Figure 8. Monoterpenoids in Icacinaceae secologanin-tryptamine derived alkaloids.

Yohimbine (104), also from the bark of C.johimbe K Schum. and from the roots of R. serpentina (1. ) Benth. has a folk history (unsubstantiated) of use as an aphrodisiac. Its use has been confirmed experimentally as a local anesthetic, with occasional employment for rehef ia angiaa pectoris and arteriosclerosis, but is frequently contraindicated by its undesired renal effects. Yohimbine and some of its derivatives have been reported as hahuciaogenic (70). In addition, its pattern of pharmacological activities ia a variety of animal models is so broad that its general use is avoided. All ten carbon atoms of secologanin (102) as well as the entire skeleton of tryptamine (98, R = H) are clearly seen as iatact portions of this alkaloid. 

Indole alkaloids from Tabernaemontana plants are all biogenetically derived from tryptophan (tryptamine) and secologanine, which constitute the indole and terpenic portions, respectively, and can be classified into nine main types depending on the structural characteristics of their skeleton (Fig. 1). 

Leonard, J. 1999. Recent progress in the chemistry of monoterpenoid alkaloids derived from secologanin. Nature Product Reports, 16 319-338. 

Strictosidine synthetase catalyzes the stereospecific condensation of trypt-amine and the iridoid glucoside secologanin to form strictosidine. The product is the precursor of the monoterpenoid-derived indole and quinoline alkaloids. 

All terpenoid indole alkaloids are derived from tryptophan and the iridoid terpene secologanin (Fig. 2b). Tryptophan decarboxylase, a pyridoxal-dependent enzyme, converts tryptophan to tryptamine (62, 63). The enzyme strictosidine synthase catalyzes a stereoselective Pictet-Spengler condensation between tryptamine and secologanin to yield strictosidine. Strictosidine synthase (64) has been cloned from the plants C. roseus (65), Rauwolfla serpentine (66), and, recently, Ophiorrhiza pumila (67). A crystal structure of strictosidine synthase from R. serpentina has been reported (68, 69), and the substrate specificity of the enzyme can be modulated (70). 

The basic stmcture of monoterpenoid indole alkaloids includes an indole nucleus derived from tryptophan via tryptamine (L) and a versatile C9 or CIO unit arising from the monoterpenoid secologanin (LI). Strictosidine synthase catalyzes the synthesis of strictosidine (LII) from tryptamine and secologanin (Scheme XXIV) [76],... 

Beke et al. (115) have reported the preparation of the 19-type alkaloids from secologanin (132) by Pictet-Spengler reaction with phenethylamine derivatives. They have also reviewed the regio- and stereoselectivity in the formation of the ipecosane alkaloids (22). 

Ibrahim 407) has reported a microbial transformation of emetine (1) into O-methylpsychotrine (4), which used Cunninghamella blakesleeana MR-198. The first synthesis of the alkaloid glucoside neoalangiside (48) has been achieved with the Aimi et al. 408). It started with the condensation of the brominated phenethylamine 196 with the tetra-O-acetyl derivative of secologanin (132) and proceeded through the intermediates 197 and 198. 

Biosynthesis (Chapter 6).— E>etailed studies have been reported with individual enzymes responsible for the early stages of terpenoid biosynthesis. The mechanism whereby two molecules of famesyl pyrophosphate couple to furnish squalene is still uncertain and the structure of the C30 pyrophosphate intermediate isolated by Rilling in 1966 remains elusive. The genesis of the monoterpenoid portion of the indole alkaloids has been intensively studied. Of special interest was the discovery of the bismonoterpenoid foliamenthin, which is a derivative of the indole alkaloid precursor secologanin. The biosynthesis of the gibberellins has received detailed attention on both sides of the Atlantic. nr-kaurene, the parent, is formed via geranylgeranyl pyrophosphate and enr-copalyl pyrophosphate and this seems to follow a... 

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